Phenyl-substituted 9-deoxy-6,9α-epoxymethano-PG analogs

ABSTRACT

Processes for preparing prostacyclin analogs which are 9-deoxy-6,9-epoxymethano derivatives of prostaglandin F 1 α -type compounds, illustrated, for example, by a compound of the formula ##STR1## wherein ˜ indicates alpha or beta configuration; including the products and intermediates produced therein, said products having pharmacological utility.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a divisional application of Ser. No. 788,145,filed Apr. 19, 1977, now issued as U.S. Pat. 4,180,569, on Dec. 19,1978.

The present invention relates to prostaglandin analogs for which theessential material constituting a disclosure therefor is incorporated byreference here from U.S. Pat. 4,130,569.

I claim:
 1. A cyclic ether of the formula ##STR2## wherein L is (1) avalence bond, (2) --(CH₂)_(d) -- wherein d is one to 5 inclusive, (3)--(CH₂)_(t) --CF₂ -- wherein t is 2, 3, or 4, (4) --CH₂ --CH═CH--A--wherein A is a valence bond or --(CH₂)_(h) -- wherein h is one, 2, or 3,or (5) --CH₂ --O--CH₂ --Y-- wherein Y is a valence bond or --(CH₂)_(k)-- wherein k is one or 2; wherein Q₂ is ##STR3## wherein R₃ is hydrogenor alkyl of one to 4 carbon atoms, inclusive; wherein R₅ and R₆ arehydrogen, alkyl of one to 4 carbon atoms, inclusive, or fluoro, beingthe same or different, with the proviso that one of R₅ and R₆ is fluoroonly when the other is hydrogen or fluoro, and the further proviso thatneither R₅ nor R₆ is fluoro when Z is oxa (--O--);wherein R₂₁ is##STR4## wherein R₆₀ is (a) hydrogen, (b) alkyl of one to 12 carbonatoms, inclusive, or (c) a pharmacologically acceptable cation; whereinT is alkyl of one to 4 carbon atoms, inclusive, fluoro, chloro,trifluoromethyl, or --OR₇ wherein R₇ is alkyl of one to 4 carbon atoms,inclusive, and s is zero, one, 2, or 3, with the proviso that not morethan two T's are other than alkyl and when s is 2 or 3 the T's areeither the same or different; wherein X is cis-- or trans--CH═CH--,--C.tbd.C-- or --CH₂ CH₂ --; wherein Z represents an oxa atom (--O--) orC_(j) H_(2j) wherein C_(j) H_(2j) is a valence bond or alkylene of oneto 9 carbon atoms, inclusive, substituted with zero, one, or 2 fluoro,with one to 6 carbon atoms, inclusive between --CR₅ R₆ -- and the phenylring; and wherein the wavy line (˜) indicates attachment in cis or transconfiguration.
 2. A compound according to claim 1 wherein X istrans--CH═CH--.
 3. A compound according to claim 2 wherein Q₂ is##STR5## wherein R₃ is hydrogen, methyl, or ethyl.
 4. A compoundaccording to claim 3 wherein R₂₁ is ##STR6##
 5. A compound according toclaim 4 wherein L is --(CH₂)_(d) -- wherein d is one to 5 inclusive. 6.A compound according to claim 5 wherein ##STR7##
 7. A compound accordingto claim 6 wherein s is zero. 8.9-Deoxy-6ξ,9α-epoxymethano-16-phenoxy-17,18,19,20-tetranor-PGF₁, lesspolar isomer and more polar isomer, compounds according to claim
 7. 9.9-Deoxy-6ξ,9α-epoxymethano-16-phenoxy-17,18,19,20-tetranor-PGF₁, methylester, less polar isomer and more polar isomer, compounds according toclaim
 7. 10. A compound according to claim 5 wherein ##STR8##
 11. Acompound according to claim 10 wherein s is zero. 12.9-Deoxy-6ξ,9α-epoxymethano-17-phenyl-18,19,20-trinor-PGF₁, less polarisomer and more polar isomer, compounds according to claim
 11. 13.9-Deoxy-6ξ,9.alpha.-epoxymethano-17-phenyl-18,19,20-trinor-PGF₁, methylester, less polar isomer and more polar isomer, compounds according toclaim
 11. 14. A compound according to claim 4 wherein L is --(CH₂)_(t)--CF₂ -- wherein t is 2, 3, or
 4. 15. A compound according to claim 4wherein L is --CH₂ --O--CH₂ --Y-- wherein Y is a valence bond or--(CH₂)_(k) -- wherein k is one or
 2. 16. A compound according to claim3 wherein R₂₁ is ##STR9##